{
  "abstract": "Background\n\nEarly diagnosis of paediatric lower respiratory tract infection (LRTI) in intensive care is difficult because clinical features overlap with non-infectious respiratory failure and conventional microbiology has limited sensitivity. We aimed to integrate airway microbial and host-response signals to identify early diagnostic biomarkers in mechanically ventilated children.Methods\n\nWe re-analysed airway metagenomic sequencing and tracheal aspirate transcriptomics from 261 ventilated paediatric intensive care unit (PICU) patients using differential expression, protein-protein interaction network analysis, and machine-learning feature selection. Findings were evaluated in an exploratory assessment of biologically related cytokine markers within an independent prospective cohort (RASCALS; n = 100 enrolled, n = 78 analysed) using non-bronchoscopic mini-bronchoalveolar lavage (mini-BAL), plasma cytokines, and clinician-adjudicated diagnoses.Results\n\nRespiratory syncytial virus and Haemophilus influenzae were the only pathogens consistently enriched in LRTI. Host transcriptomics showed activation of interferon, cytokine, and chemokine signalling. Network-guided feature selection identified a seven-gene panel (IRF7, FFAR3, GZMB, FABP4, FN1, CXCL5, BCAR1) with high diagnostic performance in cross-validation (median F1 0.94), comparable to a published 14-gene model. In RASCALS, a logistic model using mini-BAL IL-1β, IL-4, and IL-8 classified bacterial LRTI with 65% accuracy (sensitivity 70%, specificity 63%), while blood IL-6 and TRAIL achieved 82% accuracy (sensitivity 79%, specificity 83%).Conclusions\n\nIntegrating airway microbial profiles with host-response biomarkers supports earlier and more specific LRTI diagnostic classification in ventilated children. The seven-gene panel and cytokine combinations are candidates for rapid PCR- or immunoassay-based bedside tests to inform antimicrobial stewardship.",
  "abstract_shown": true,
  "affiliations": [
    "Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.",
    "Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.",
    "Milner Therapeutics Institute, University of Cambridge, Cambridge, UK. gy260@cam.ac.uk.",
    "Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK. gy260@cam.ac.uk.",
    "Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. gy260@cam.ac.uk.",
    "Department of Quantum Information, Institute for Convergence Science Academy, Yonsei University, Seoul, Republic of Korea. gy260@cam.ac.uk.",
    "Department of Paediatrics, University of Cambridge, Cambridge, UK.",
    "Paediatric Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK.",
    "Milner Therapeutics Institute, University of Cambridge, Cambridge, UK. nh417@cam.ac.uk.",
    "Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK. nh417@cam.ac.uk.",
    "Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. nh417@cam.ac.uk.",
    "Department of Quantum Information, Institute for Convergence Science Academy, Yonsei University, Seoul, Republic of Korea. nh417@cam.ac.uk.",
    "Department of Nano Biomedical Engineering (NanoBME), Advanced Science Institute, Yonsei University, Seoul, Republic of Korea. nh417@cam.ac.uk.",
    "Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, Republic of Korea. nh417@cam.ac.uk."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Zongtai Wu"
    },
    {
      "affs": [
        2,
        3,
        4,
        5
      ],
      "name": "Gehad Youssef"
    },
    {
      "affs": [
        6
      ],
      "name": "Iain R L Kean"
    },
    {
      "affs": [
        6
      ],
      "name": "Zhenguang Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "John A Clark"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Nazima Pathan"
    },
    {
      "affs": [
        8,
        9,
        10,
        11,
        12,
        13
      ],
      "name": "Namshik Han"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/89hq3jnef4n5n.bib",
  "cited_by": 0,
  "doi": "10.1186/s12931-026-03829-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13721528",
  "id": "89hq3jnef4n5n",
  "issns": [
    "1465-9921",
    "1465-993X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958270",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7171439689",
  "pdf_url": "https://europepmc.org/articles/PMC13721528?pdf=render",
  "pmcid": "PMC13721528",
  "pmid": "42958270",
  "published": "2026-07-27",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/89hq3jnef4n5n.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:48Z",
      "native_id": "MED:42958270",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958270"
    },
    {
      "first_seen": "2026-11-03T12:22:12Z",
      "native_id": "PMC13721528",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12931-026-03829-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Integrated host-microbe biomarkers for early diagnostic classification of paediatric LRTI in mechanically ventilated children.",
  "title_text": "Integrated host-microbe biomarkers for early diagnostic classification of paediatric LRTI in mechanically ventilated children.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:12Z",
  "url": "https://research.draconitic.com/paper/89hq3jnef4n5n",
  "venue": "Respiratory research",
  "versions": []
}